L-742001

L-742001 is a synthetic small-molecule diketo acid inhibitor of the influenza A virus PA endonuclease, an essential metal-dependent endonuclease subdomain of the viral RNA-dependent RNA polymerase complex that mediates “cap-snatching” from host pre-mRNAs to prime viral mRNA synthesis.[3][4][6][8] By chelating the two-metal catalytic core and engaging multiple residues within the PA endonuclease active site, L-742001 potently inhibits endonuclease activity (IC50 ~0.5 μM) and reduces influenza A viral replication in cell culture and in mouse models, establishing this chemotype as a prototype scaffold for influenza endonuclease-targeted antivirals.[3][4][6][8] Originally discovered in the 1990s and reported by Merck as an early RNA polymerase/PA inhibitor lead, L-742001 showed strong antiviral activity but was ultimately deemed unsuitable for further clinical development; however, its structural and resistance profiles have been widely used to map PA active-site interactions and guide the design of newer influenza endonuclease inhibitors.[3][6][8][9]

Other names

L-742001 hydrochlorideL742001 hydrochlorideL 742001 hydrochloride